Asthma and lower airway disease
Increased sputum and bronchial biopsy IL-13 expression in severe asthma

https://doi.org/10.1016/j.jaci.2008.01.005Get rights and content

Background

The importance of IL-13 in the asthma paradigm is supported by increased expression in human subjects, particularly in patients with mild-to-moderate asthma. However, the role of IL-13 in severe asthma needs to be further defined.

Objective

We sought to assess IL-13 expression in sputum and bronchial biopsy specimens from subjects with mild-to-severe asthma.

Methods

Sputum IL-13 concentrations were measured in 32 control subjects, 34 subjects with mild asthma, 21 subjects with moderate asthma, and 26 subjects with severe asthma. Enumeration of mast cells, eosinophils, and IL-13+ cells in the bronchial submucosa and airway smooth muscle (ASM) bundle was performed in 7 control subjects, 14 subjects with mild asthma, 7 subjects with moderate asthma, and 7 subjects with severe asthma.

Results

The proportion of subjects with measurable IL-13 in the sputum was increased in the mild asthma group (15/34) and severe asthma group (10/26) compared with that seen in the control group (4/32; P = .004). IL-13+ cells were increased within the submucosa in all asthma severity groups compared with control subjects (P = .006). The number of IL-13+ cells were increased within the ASM bundle in the severe asthma group compared with that seen in the other groups (P < .05). Asthma control questionnaire scores positively correlated with sputum IL-13 concentrations (Rs = 0.35, P = .04) and mast cells in the ASM bundle (Rs = 0.7, P = .007). IL-13+ cells within the submucosa and ASM correlated with sputum eosinophilia (Rs = 0.4, P ≤ .05).

Conclusions

IL-13 overexpression in sputum and bronchial biopsy specimens is a feature of severe asthma.

Section snippets

Subjects

Subjects were recruited from local primary health care providers, respiratory clinics, hospital staff, and through local advertising. Asthma was defined and severity categorized by using international (Global Initiative for Asthma [GINA]) guidelines15 and American Thoracic Society criteria for refractory asthma.14 Healthy subjects had no history of respiratory symptoms and normal spirometric results. All subjects provided written informed consent, with study approval from the Leicestershire

Results

Clinical and sputum characteristics for subjects in cohort 1 are shown in Table I. The groups with asthma were well matched for AHR and sputum eosinophilic inflammation. The sputum IL-13 concentration for each subject is shown in Fig 1. The proportion of subjects with measurable IL-13 in their sputum supernatant was increased in those with severe asthma (10/26) and mild asthma (15/34) compared with the proportion of healthy control subjects (4/32, P < .05). In addition, the proportion of

Discussion

For the first time, we have shown that sputum IL-13 concentration and the number of IL-13+ cells in the bronchial submucosa and ASM bundle were increased in severe asthma. We have confirmed our earlier observation that mast cell localization to the ASM bundle is a feature of mild asthma2 and demonstrated for the first time that this is also characteristic of moderate and severe refractory disease. Interestingly, in contrast to severe asthma, increased sputum IL-13 concentrations and IL-13+

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    Supported by Asthma UK, Cambridge Antibody Technology, GlaxoSmithKline, and a DOH Clinical Scientist award.

    Disclosure of potential conflict of interest: C. E. Brightling has consulting arrangements with AstraZeneca, GlaxoSmithKline, Cambridge Antibody Technology, and Roche; has received research support from AstraZeneca, Cambridge Antibody Technology, and GlaxoSmithKline; and is on the speakers' bureau for GlaxoSmithKline, AstraZeneca, and Pfizer. R. May is employed by and has equity in Cambridge Antibody Technology. P. Monk is employed by Synairgen Research Ltd. I. D. Pavord has received research support from GlaxoSmithKline and AstraZeneca. The rest of the authors have declared that they have no conflict of interest.

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